Spatially addressable combinatorial

Pirrung, M.C., Spatially addressable combinatorial libraries, Chem. Rev., 1997, 97, 473-488. 

Figure 3 Spatially addressable combinatorial peptide library comprised of 125 peptides with the sequence of XCysYCysZCysGly, whereby X, Y, and Z are spacer residues of a-Glu, y-Glu, GABA, SerGly, and e-aminohexanoic acid (s-Ahx). (Reproduced...

W. K. Goetzinger, and J. N. Kyranos, Fast gradient RP-HPLC for high throughput quality control analysis of spatially addressable combinatorial libraries, Am. Lab. 30 (1998), 27-37. 

Pirrung MC. Spatially Addressable combinatorial libraries. Chem Rev. 1997 97 473-188. 

Several considerations drive the design and synthesis of spatially addressable, combinatorial arrays (25). The selection of building blocks and backbone... 

Goetzinger, W.K. Kyranos, J.N. Fast Gradient RP-HPLC for High-throughput Quality Control Analysis of Spatially Addressable Combinatorial Libraries, Am. Lab. 30, 27-37 (1998). 

Several combinatorial approaches to the discovery of transition metal based catalysts for olefin polymerization have been described. In one study Brookhart-type polymer-bound Ni- and Pd-(l,2-diimine) complexes were prepared and used in ethylene polymerization (Scheme 3).60,61 A resin-bound diketone was condensed with 48 commercially available aminoarenes having different steric properties. The library was then split into 48 nickel and 48 palladium complexes by reaction with [NiBr2(dme)] and [PdClMe(COD)], respectively, all 96 pre-catalysts being spatially addressable. 

As first practiced by Geysen and Houghton, the preparation of combinatorial libraries produced discrete compounds of known identity through a technique known as "spatial separation," which simply means that individual compounds in the library are produced discretely and are not mixtures. Such spatially addressable compound sets are produced in such a way as to keep separate the reaction flasks or resin beads containing the individual components of the library and perform bioassays on the discrete compounds, one at a time. Thus, if the "history" of the reaction conditions performed in each flask or on each solid support, the identity of the compounds produced is known, without resort to structure elucidation techniques. Initially, this technique, after typically an extensive reaction development stage, allowed the preparation of between 10 and 1000 discrete combinatorial products. 

Parallel synthesis is the term loosely applied to the preparation of discrete compounds in the format of a spatially addressable array. It is often used in contrast to "mixture-based" combinatorial synthesis. While it is hue that the term "parallel synthesis" may encompass the preparation of a fully combinatorial multidimensional array of compounds, in practice, it most... 

In-situ photofabrication of OND arrays involves light-directed, spatially addressable, parallel (combinatorial) chemical synthesis [35,43,66-68]. A surface, usually a sihcon wafer or a glass slide, is coated with hnker molecules... 

The use of planar supports for presenting large arrays of spatially addressed molecules is one of the most powerful and versatile methods for creating combinatorial libraries.19,28-29... 

In this chapter we will discuss current approaches for analytical characterization of combinatorial libraries in a pharmaceutical industry environment. Recently, several analytical groups have presented very similar strategies for analysis of libraries [7-9]. As will be shown later, the key to successful analytical characterization of a combinatorial library is to perform analytical and chemical work in parallel with the library development. The accumulation of data and analytical experience during this process results in an assessment of library quality with a high level of confidence, even if as little as 5-10% of the library components are analyzed. Utilization of the strategy will be demonstrated using two examples analysis of a library synthesized on a robotic station in spatially addressed format and analysis of a library synthesized in accordance with split-and-mix technology. 

Therefore, heterogeneous catalysts present a greater potential for the application of HT and Combinatorial methods, because they involve diverse compositional phases that are usually formed by interfacial reactions during their synthesis, which in turn produce a variety of structural and textural properties, often too vast to prepare and test by traditional methods. In this respect the HT and Combinatorial methods extend the capabilities of the R D cycle, which comprises the synthesis, the characterization of physicochemical properties and the evaluation of catalytic properties. The primary screening HT method gives the possibility of performing a rapid test of hundreds or thousands of compounds using infrared detection methods [27-29]. Alternatively, a detection method called REMPI (Resonance Enhanced Multi Photon Ionization) has been used, which consists of the in situ ionization of reaction products by UV lasers, followed by the detection of the photoions or electrons by spatially addressable microelectrodes placed in the vicinity of the laser beam [30, 31]. 

Scharn, D., Wenschuh, H., Reineke, U., Mergener, J.S., and Germeroth L. 2002. Spatially addressed synthesis of amino- and amino-oxy-substituted 1,3,5-triazine arrays on polymeric membranes. Journal of Combinatorial Chemistry, 2 361-69. 

In essence only two approaches exist to generate combinatorial peptide libraries biologic and synthetic library approaches. According to the different techniques used, the synthetic library approach can be divided additionally into five methods 1) the spatially addressable parallel library method (1, 4, 8),... 

Other methods that are used commonly in combinatorial chemistry include attaching structures of known composition to polystyrene beads (one compound per bead) or synthesizing structures onto a inienxthip-sized matrix where a compound s location gives its identity. Tlie latter is called spatially addressable synthesis. This topic is covered in more detail in Chapter 3. 

Spatially addressed synthesis is yet another alternative. This does not play an important role in general combinatorial chemistry, but has been used successfully used in biochip applications such as in DNA -probe technology. 

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